Base-Promoted Tandem Cyclization of 2-(Indol-3-yl)naphthoquinones with Benzamidines toward Polysubstituted Pyrimido[4,5-b]indoles.

A novel and unique approach for the construction of polysubstituted pyrimido[4,5-b]indoles from 2-(indol-3-yl)naphthoquinones and benzamidines is described. Our strategy, promoted by an inorganic base, involves the ring opening and recyclization of naphthoquinone and produces three nitrogen heterocyclic rings via multiple C-N bond formations in one pot under transition-metal-free conditions.

Multi-omics analyses reveal aberrant differentiation trajectory with WNT1 loss-of-function in type XV osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a group of severe genetic bone disorders characterized by congenital low bone mass, deformity, and frequent fractures. Type XV OI is a moderate to severe form of skeletal dysplasia caused by WNT1 variants. In this cohort study from southern China, we summarized the clinical phenotypes of patients with WNT1 variants and found that the proportion of type XV patients was around 10.3% (25 out of 243) with a diverse spectrum of phenotypes. Functional assays indicated that variants of WNT1 significantly impaired its secretion and effective activity, leading to moderate to severe clinical manifestations, porous bone structure, and enhanced osteoclastic activities. Analysis of proteomic data from human skeleton indicated that the expression of SOST (sclerostin) was dramatically reduced in type XV patients compared to patients with COL1A1 quantitative variants. Single-cell transcriptome data generated from human tibia samples of patients diagnosed with type XV OI and leg-length discrepancy, respectively, revealed aberrant differentiation trajectories of skeletal progenitors and impaired maturation of osteocytes with loss of WNT1, resulting in excessive CXCL12+ progenitors, fewer mature osteocytes, and the existence of abnormal cell populations with adipogenic characteristics. The integration of multi-omics data from human skeleton delineates how WNT1 regulates the differentiation and maturation of skeletal progenitors, which will provide a new direction for the treatment strategy of type XV OI and relative low bone mass diseases such as early onset osteoporosis.

Osteogenesis imperfecta is a rare disease characterized by low bone mass, frequent fractures, and long bone deformity. Type XV osteogenesis imperfect is an autosomal recessive disorder caused by WNT1 variants, while heterozygous variants of WNT1 result in early onset osteoporosis. In this cohort study, we summarized the clinical features of 25 patients diagnosed with type XV osteogenesis imperfect. The WNT1 variants were confirmed by genetic test. Molecular assays were conducted to reveal the impact of variants on WNT1 protein activity and bone structure. We then compared the protein levels in bone tissues isolated from the type XV patients and patients with mild deformity using proteomic method, and found that the expression of SOST, mainly produced by mature osteoblasts and osteocytes, was dramatically reduced in type XV patients. We further compared the global mRNA expression levels in the skeletal cells using single-cell RNA sequencing. Analyses of these data indicated that more immature progenitors were identified and maturation of osteocytes was impaired with WNT1 loss-of-function. Our study helps to understand the underlying pathogenesis of type XV osteogenesis imperfecta.

Single-trial interindividual correlation shows semantic and visuospatial networks are fundamental for advanced mathematical learning.

Mathematical learning and ability are crucial for individual and national economic and technological development, but the neural mechanisms underlying advanced mathematical learning remain unclear. The current study used functional magnetic resonance imaging (fMRI) to investigate how brain networks were involved in advanced mathematical learning and transfer. We recorded fMRI data from 24 undergraduate students as they learned the advanced mathematical concept of a commutative mathematical group. After learning, participants were required to complete learning and transfer behavioural tests. Results of single-trial interindividual brain-behaviour correlation analysis found that brain activity in the semantic and visuospatial networks, and the functional connectivity within the semantic network during advanced mathematical learning were positively correlated with learning and transfer effects. Additionally, the functional connectivity between the semantic and visuospatial networks was negatively correlated with the learning and transfer effects. These findings suggest that advanced mathematical learning relies on both semantic and visuospatial networks.

The interconnection of orthographic, phonetic, and semantic skills with arithmetic fluency.

Arithmetic fluency is considered considers highly rely on language processing, encompassing essential skills. However, the independent predictive power of phonetic, semantic, or orthographic skills in relation to arithmetic fluency remains an unresolved query. This study introduces the common component hypothesis to elucidate the inconsistent findings in previous research. The hypothesis posits that significant correlations between language and mathematics hinge on whether the language and mathematics utilized in a given task share a common component. According to this hypothesis, processing skills for each of the three fundamental language elements (i.e., phonetic, semantic, orthographic) should correlate with arithmetic fluency, as these elements are also integral to simple arithmetic processing. A cohort of one hundred and ninety-eight primary school students participated in the study, undertaking a battery of tests assessing general cognitive abilities, psycholinguistic elements, and arithmetic fluency. The results showed that orthographic, phonetic, and semantic abilities independently predicted arithmetic fluency, even after accounting for all other cognitive predictors. These findings substantiate the common component hypothesis, providing empirical support for explaining the association between language and mathematics. This evidence contributes to addressing the interplay between language and mathematics in educational contexts.

Behavior-related potentials from single-trial interindividual correlation between event related potentials and behavioral performance reveals right lateralized processing of numerosity.

Accumulated functional magnetic resonance imaging (fMRI) and electroencephalography evidence indicate that numerosity is first processed in the occipito-parietal cortex. fMRI evidence also indicates right-lateralized processing of numerosity, but there is no consistent evidence from event-related potential (ERP) studies. This study investigated the ERP of numerosity processing in the left, right, and bilateral visual fields. The single-trial ERP-behavioral correlation was applied to show how the ERP was associated with behavioral responses. The results showed a significant early behavioral-ERP correlation on the right N1 component when stimuli were presented in the left visual field rather than in the right visual field. The behavioral ERP correlation was termed BN1. There was bilateral BN1 based on the reaction time or error rate, but the right BN1 was larger than that the left BN1 when the stimulus was present in the bilateral visual field. Therefore, this study provided a new neural marker for individual differences in processing numerosity and suggested that processing numerosity was supported by the right occipito-parietal cortex.

Number sense-arithmetic link in Grade 1 and Grade 2: A case of fluency.

BACKGROUND: Recent research suggested fluent processing as an explanation on why number sense contributes to simple arithmetic tasks-'Fluency hypothesis'. AIMS: The current study investigates whether number sense contributes to such arithmetic tasks when other cognitive factors are controlled for (including those that mediate the link); and whether this contribution varies as a function of participants' individual maths fluency levels. SAMPLE: Four hundred and thirty-seven Chinese schoolchildren (186 females; Mage = 83.49 months) completed a range of cognitive measures in Grade 1 (no previous classroom training) and in Grade 2 (a year later). METHODS: Number sense, arithmetic (addition and subtraction), spatial ability, visuo-spatial working memory, perception, reaction time, character reading and general intelligence were measured. RESULTS: Our data showed that the link between number sense and arithmetic was weaker in Grade 1 (Beta = .15 for addition and .06 (ns) for subtraction) compared to Grade 2 (.23-.28), but still persisted in children with no previous maths training. Further, math's performance in Grade 1 did not affect the link between number sense and maths performance in Grade 2. CONCLUSION: Our data extended previous findings by showing that number sense is linked with simple maths task performance even after controlling for multiple cognitive factors. Our results brought some evidence that number sense-arithmetic link is somewhat sensitive to previous formal maths education. Further research is needed, as the differences in effects between grades were quite small, and arithmetic in Grade 1 did not moderate the link at question in Grade 2.

Form perception is a cognitive correlate of the relation between subitizing ability and math performance.

"Subitizing" defines a phenomenon whereby approximately four items can be quickly and accurately processed. Studies have shown the close association between subitizing and math performance, however, the mechanism for the association remains unclear. The present study was conducted to investigate whether form perception assessed on a serial figure matching task is a potential non-numerical mechanism between subitizing ability and math performance. Three-hundred and seventy-three Chinese primary school students completed four kinds of dot comparison tasks, serial figure matching task, math performance tasks (including three arithmetic computation tasks and math word problem task), and other cognitive tasks as their general cognitive abilities were observed as covariates. A series of hierarchical regression analyses showed that after controlling for age, gender, nonverbal matrix reasoning, and visual tracking, subitizing comparison (subitizing vs. subitizing, subitizing vs. estimation) still contributed to simple addition or simple subtraction but not to complex subtraction ability or math word problem. After taking form perception as an additional control variable, the predictive power of different dot comparison conditions disappeared. A path model also showed that form perception fully mediates the relation between numerosity comparison (within and beyond the subitizing range) and arithmetic performance. These findings support the claim that form perception is a non-numerical cognitive correlate of the relation between subitizing ability and math performance (especially arithmetic computation).

Verbalized arithmetic principles correlate with mathematics achievement.

BACKGROUND: When mathematical knowledge is expressed in general language, it is called verbalized mathematics. Previous studies on verbalized mathematics typically paid attention to mathematical vocabulary or educational practice. However, these studies did not exclude the role of symbolic mathematics ability, and almost no research has focused on verbalized mathematical principles. AIMS: This study is aimed to investigate whether verbalized mathematics ability independently predicts mathematics achievement. The current study hypothesized that verbalized mathematics ability supports mathematics achievement independent of general language, related cognitive abilities and even symbolic mathematical ability. SAMPLE: A sample of 241 undergraduates (136 males, 105 females, mean age = 21.95, SD = 2.38) in Beijing, China. METHODS: A total of 12 tests were used, including a verbalized arithmetic principle test, a mathematics achievement test, and tests on general language (sentence completion test), symbolic mathematical ability (including symbolic arithmetic principles test, simple arithmetic computation and complex arithmetic computation), approximate number sense ability (numerosity comparison test) and several related cognitive covariates (including the non-verbal matrix reasoning, the syllogism reasoning, mental rotation, figure matching and choice reaction time). RESULTS: Results showed that the processing of verbalized arithmetic principles displayed a significant role in mathematics achievement after controlling for general language, related cognitive abilities, approximate number sense ability and symbolic mathematics ability. CONCLUSIONS: The results suggest that verbalized mathematics ability was an independent predictor and provided empirical evidence supporting the verbalized mathematics role on achievement as an independent component in three-component mathematics model.

The structure correspondence hypothesis predicts how word and sentence in language correlate with term and principle in mathematics.

The association between language and mathematics is an important debated topic. Here, we proposed a structure correspondence hypothesis to explain under what conditions language and mathematics are closely related. According to the hypothesis, there would be an association when they have equivalent structure. One hundred and fifty high school students were recruited to finish mathematical and language tests at the element level (i.e., geometric term processing and word analogy) and at the low-dimensional combination level (i.e., geometric principle processing and sentence completion) as well as the tests to measure cognitive covariates (general intelligence and spatial processing). After controlling for age, gender and cognitive covariates, geometric term processing and word analogy were closely correlated, and geometric principle processing and sentence completion were significantly correlated. No other correlations were found. The results support the structure correspondence hypothesis and provide a new perspective of structure of language and verbalized mathematics for the relation between language and mathematics.

Different cognitive mechanisms used for solving open and closed math problems.

Problem-solving skills are very important in our daily life. Almost all problem-solving studies have addressed the cognitive correlates of solving closed problems, but only limited studies have investigated the cognitive mechanisms of solving open problems. The current study aimed to systematically examine differences between the cognitive mechanisms used for solving open and closed problems. In total, the abilities of 142 high school students to solve open and closed problems were assessed, as were a series of general cognitive abilities as controlled variates. Analogical reasoning uniquely contributed to solving both open and closed math problems, after controlling for age, gender, and inductive reasoning. Reactive cognitive flexibility (measured using the Wisconsin card sorting test) and spatial working memory uniquely correlated only with solving open and closed math problems, respectively. These findings suggest that the cognitive processes used to solve open and closed math problems differ. Open and closed math problems appear to require more reactive cognitive flexibility for generation and more memory for retrieval, respectively.

High-definition transcranial direct current stimulation (HD-tDCS) of the left middle temporal gyrus (LMTG) improves mathematical reasoning.

The role of the visuospatial network in mathematical processing has been established, but the role of the semantic neural network in mathematical processing is still poorly understood. The current study used high-definition transcranial direct current stimulation (HD-tDCS) to examine whether the semantic network supports mathematical processing. Using a single-blind, randomized, sham-controlled experimental design, 48 participants were randomly assigned to receive either anodal or sham HD-tDCS on the left middle temporal gyrus (LMTG), a core region of the semantic network. A number series completion task was used to measure mathematical reasoning and an arithmetical computation task was used as a control condition. Both tasks were administered before and after the 20 min HD-tDCS. The results showed that anodal HD-tDCS on the LMTG enhanced performance on the number series completion task, but not on the arithmetical computation task. Trial-level analysis further showed greater improvement at the more difficult problems of the number series completion task. These results demonstrate that the semantic network plays an important role in mathematical processing.

Verbal but not visual-spatial working memory contributes to complex arithmetic calculation.

The contribution of working memory to mathematics has been extensively studied. It has been proposed that verbal working memory (VWM) and visual-spatial working memory (VSWM) have distinct contributions, but results have been inconclusive. Here, we hypothesized that VWM and VSWM contribute differentially to separate sub-domains of mathematics. To test this hypothesis, we enrolled 199 primary school students and measured their VWM and VSWM with number/letter/matrix backward span tasks, and tested mathematics performance with simple subtraction, complex subtraction, multi-step calculation and number series completion, while controlling for several aspects of cognition. We found that while letter backward span had a significant contribution to complex subtraction, multi-step computation and number series completion, number backward span only had a significant contribution to multi-step computation, and matrix span had no effect on any math task. These results suggest that only VWM associated with complex mathematics, which might reflect verbal rehearsal. In contrast, VSWM does not appear to associated with mathematics.

The involvement of the semantic neural network in rule identification of mathematical processing.

The role of the visuospatial network in mathematical processing has been established, but the involvement of the semantic network in mathematical processing is still poorly understood. The current study utilized a number series completion paradigm with the event-related potential (ERP) technique to examine whether the semantic network supports mathematical processing and to find the corresponding spatiotemporal neural marker. In total, 32 right-handed undergraduate students were recruited and asked to complete the number series completion as well as the arithmetical computation task in which numbers were presented in sequence. The event-related potential and multi-voxel pattern analysis showed that the rule identification process involves more semantic processing when compared with the arithmetical computation processes, and it elicited higher amplitudes for the late negative component (LNC) in left frontal and temporal lobes. These results demonstrated that the semantic network supports the rule identification in mathematical processing, with the LNC acting as the neural marker.

The developmental relationship between nonsymbolic and symbolic fraction abilities.

A fundamental research question in quantitative cognition concerns the developmental relationship between nonsymbolic and symbolic quantitative abilities. This study examined this developmental relationship in abilities to process nonsymbolic and symbolic fractions. There were 99 6th graders (Mage = 11.86 years), 101 10th graders (Mage = 15.71 years), and 102 undergraduate and graduate students (Mage = 21.97 years) participating in this study, and their nonsymbolic and symbolic fraction abilities were measured with nonsymbolic and symbolic fraction comparison tasks, respectively. Nonsymbolic and symbolic fraction abilities were significantly correlated in all age groups even after controlling for the ability to process nonsymbolic absolute quantity and general cognitive abilities, including working memory and inhibitory control. Moreover, the strength of nonsymbolic-symbolic correlations was higher in 6th graders than in 10th graders and adults. These findings suggest a weakened association between nonsymbolic and symbolic fraction abilities during development, and this developmental pattern may be related with participants' increasing proficiency in symbolic fractions.

Academic achievement is more closely associated with student-peer relationships than with student-parent relationships or student-teacher relationships.

Introduction: Personal relationships have long been a concern in education. Most studies indicate that good personal relationships are generally positively correlated with academic performance. However, few studies have compared how different types of personal relationships correlate with academic performance, and the conclusions of existing studies are inconsistent. Based on a large sample, the current study compared how the three closest types of personal relationships among students (with parents, teachers, and their peers) compared with their academic performance. Methods: Cluster sampling was used to issue questionnaires to students in Qingdao City, Shandong Province, China in 2018 (Study 1) and in 2019 (Study 2). The actual sample size included 28168 students in Study 1 and 29869 students in Study 2 (both studies, Grades 4 and 8), thus totaling 58037 students. All students completed a personal relationship questionnaire and several academic tests. Results: The results showed that: (1) the quality of personal relationships significantly and positively correlated with academic performance; (2) Among the three types of relationships tested, the quality of student-peer relationships was the most closely associated with academic achievement. Discussion: This study gives insights into future research directions in this field and also reminds educators to pay attention to the personal relationships among their students, especially peer relationships.

Altered resting-state functional connectivity in the prefrontal cortex is related to the development of dyscalculia in patients with Turner syndrome.

AIM: Patients with Turner syndrome have a high rate of developmental dyscalculia, but the underlying neurocognitive mechanisms are not well-understood. Some studies have implicated visuospatial impairments in patients with Turner syndrome, but others have focused on poor procedural skills in patients with Turner syndrome. This study used brain imaging data to test these two alternative views. METHODS: This study recruited 44 girls with Turner syndrome (mean age, 12.91 years; SD, 2.02), with 13 (29.5%) of them meeting the criterion for developmental dyscalculia, and 14 normally developing girls (mean age, 14.26 years; SD, 2.18) as a comparison group. All participants were given basic mathematical ability tests and an intelligence test and were scanned using magnetic resonance imaging. We compared patients with Turner syndrome who had dyscalculia, patients with Turner syndrome who did not have dyscalculia, and the normal controls in terms of brain structures and resting-state functional activity. RESULTS: Compared with normal controls, both groups of patients with Turner syndrome (with or without dyscalculia) showed similarly altered functional connectivity in the occipitoparietal dorsal stream. Importantly, compared with patients with Turner syndrome without dyscalculia and normal controls, patients with Turner syndrome with dyscalculia showed decreased functional connectivity between the prefrontal and the lateral occipital cortex. CONCLUSION: We concluded that both groups of patients with Turner syndrome shared visual deficits, and patients with Turner syndrome with dyscalculia had a deficit in frontal cortex-based higher cognitive processing. It is not their visuospatial deficits but rather their deficits in higher cognitive processing that are responsible for the development of dyscalculia in patients with Turner syndrome.

Differential associations between scale-free neural dynamics and different levels of cognitive ability.

As indicators of cognitive function, scale-free neural dynamics are gaining increasing attention in cognitive neuroscience. Although the functional relevance of scale-free dynamics has been extensively reported, one fundamental question about its association with cognitive ability remains unanswered: is the association universal across a wide spectrum of cognitive abilities or confined to specific domains? Based on dual-process theory, we designed two categories of tasks to analyze two types of cognitive processes-automatic and controlled-and examined their associations with scale-free neural dynamics characterized from resting-state electroencephalography (EEG) recordings obtained from a large sample of human adults (N = 102). Our results showed that resting-state scale-free neural dynamics did not predict individuals' behavioral performance in tasks that primarily engaged the automatic process but did so in tasks that primarily engaged the controlled process. In addition, by fitting the scale-free parameters separately in different frequency bands, we found that the cognitive association of scale-free dynamics was more strongly manifested in higher-band EEG spectrum. Our findings indicate that resting-state scale-free dynamics are not universal neural indicators for all cognitive abilities but are mainly associated with high-level cognition that entails controlled processes. This finding is compatible with the widely claimed role of scale-free dynamics in reflecting properties of complex dynamic systems.

The database for extracting numerical and visual properties of numerosity processing in the Chinese population.

The ability to handle non-symbolic numerosity has been recurrently linked to mathematical abilities. The accumulated data provide a rich resource that can reflect the underlying properties (i.e., dot ratio, area, convex hull, perimeters, distance, and hash) of numerosity processing. This article reports a database of numerosity processing in the Chinese population. The database contains five independent datasets with 7459, 4902, 415, 671, 414 participants respectively. For each dataset, all data were collected in the same online computerized test, examination room, professorial tester, and using the same protocols. Computational modeling method could be used to extract the dot ratio and visual properties of numerosity from five types of dot stimuli. This database enables researchers to test the theoretical hypotheses regarding numerosity processing using a large sample population. The database can also indicate the individual difference of non-symbolic numerosity in mathematical abilities.

Early neural markers for individual difference in mathematical achievement determined from rational number processing.

The neural markers for individual differences in mathematical achievement have been studied extensively using magnetic resonance imaging; however, high temporal resolution electrophysiological evidence for individual differences in mathematical achievement require further elucidation. This study evaluated the event-related potential (ERP) when 48 college students with high or low mathematical achievement (HA vs. LA) matched non-symbolic and symbolic rational numbers. Behavioral results indicated that HA students had better performance in the discretized non-symbolic matching, although the two groups showed similar performances in the continuous matching. ERP data revealed that even before non-symbolic stimulus presentation, HA students had greater Bereitschaftspotential (BP) amplitudes over posterior central electrodes. After the presentation of non-symbolic numbers, HA students had larger N1 amplitudes at 160 ms post-stimulus, over left-lateralized parieto-occipital electrodes. After the presentation of symbolic numbers, HA students displayed more profound P1 amplitudes at 100 ms post-stimulus, over left parietal electrodes. Furthermore, larger BP and N1 amplitudes were associated with the shorter reaction times, and larger P1 amplitudes corresponded to lower error rates. The BP effect could indicate preparation processing, and early left-lateralized N1 and P1 effects could reflect the non-symbolic and symbolic number processing along the dorsal neural pathways. These results suggest that the left-lateralized P1 and N1 components elicited by matching non-symbolic and symbolic rational numbers can be considered as neurocognitive markers for individual differences in mathematical achievement.

How are different math knowledge presentations associated with math anxiety?

A close relationship between math performance and math anxiety has been demonstrated, but how different presentations of mathematics are associated with math anxiety has not been investigated. This study recruited 826 elementary school students in grades 5 and 6. All students were given math trait and state anxiety questionnaires; a nonverbal matrix reasoning task; and verbalized, symbolic, and situational fraction problem-solving tasks. After data cleaning, 475 boys and 323 girls (798 in total) were included in the analysis (mean age = 11.79, SD = 0.82). Partial correlation analysis showed that students' math traits and state anxiety were more closely related to symbolic fraction problem-solving than to verbalized and situational fraction problem-solving. Mixed linear model analysis showed that math state anxiety for symbolic problem-solving was significantly greater than that for verbalized and situational problem-solving. Based on these findings, we concluded that the presentation of symbolic math is more likely to induce math anxiety than verbalized or situational math. This finding has potential practical applications in math anxiety interventions and education.